Ten Years of Pharmacotherapy Trials in the CTN: An Overview

OR: Exploring with Drugs …..And After Before

CTN Phamacotherapy Trials Opiate Dependence Buprenorphine ( ) Bup Adolescents (0010) START (0027) POATS (0030) Smoking Cessation Nicotine Replacement (0009) Methylphenidate ADHD Smokers (0029) Adolescents Buprenorphine (0010) Methylphenidate in ADHD/SUD (0028)

The Hardworking Team for CTN

CTN 001 and 002 Primary Aim: To compare the relative clinical utility of buprenorphine/naltrexone to clonidine in short- term (13 day) detoxification Inpatient study: 57 of 77 (77%) achieved success criteria in bup/ntx, 8 of 36 (22%) clonidine Outpatient study: 46 of 157 (29%) achieved success criteria in bup/ntx, 4 of 74 (5%) clonidine

Retention higher for Bup/Nx Group compared to Clonidine group

Conclusions Definitive evidence of superiority of buprenorphine/naltrexone for opiate detoxification Early win for CTN Raised “profile” buprenorphine treatment Possible to conduct high quality pharmacotherapy study with controlled medications in a high risk population in front-line treatment settings

CTN 003: Primary Aim - Compare the relative advantage of two taper schedules (7 vs. 28 days) of Suboxone following four weeks of medication stabilization

Summary and Conclusions 7-day taper associated with better outcomes at the end of the taper period indicating that a rapid discontinuation schedule is not disadvantageous Clinical and cost relevance: If patients do just as well or better with a short taper in terms of relapse and discomfort, then the cost savings of a short taper are clearly superior.

CTN 0010: Extended vs Short Term Treatment with Bup/Ntx in Opioid-Dependent Youth Will they accept it? Compare longer term rx to detox plus psychosocial trt Is it safe? What happens when buprenorphinetrt stops?

Wk 4 Wk 8 Wk 12 DTX 37% (17) 26% (11)33% (14) BUP 21% (12) 13% (7) 16% (8) P value for group effect = 0.02 Injecting Drug Use Wks 4, 8, 12

Summary Only study of agonist therapy in adolescent/young adults Primary and secondary outcomes strongly favored BUP Major implications for treatment: Life- saving treatment in an extremely high-risk group

Prescription Opioid Addiction Treatment Study (POATS) Overview n Study of treatment for prescription opioid dependence, examining n Buprenorphine of varying duration n Counseling of varying intensity n Largest treatment study ever conducted for prescription opioid dependence (N=653)

Study Schema

Phase 1 Treatment Success EMMSMMp 5.8%7.4%0.45 Phase 1 Treatment Success Criteria ≤ 4 days opioid use per month No positive urine screens for opioids on 2 consecutive weeks No other formal substance abuse treatment No injection of opioids

Phase 2 Substantial Improvement Substantial improvement Abstinent for > 3 of final 4 weeks (including final week) of bup-nx stabilization (urine-confirmed self-report) EMMSMMp Week 12 (end of stabilization) 51.7%46.7%0.3

Conclusions n Largest controlled trial prescription opioid treatment n Tapering opioids, whether initially or after a period of improvement, led to nearly universal relapse n Patients with chronic pain did as well as those without chronic pain, & many had significant improvement in their pain

Smoking Cessation Treatment With Transdermal Nicotine Replacement Therapy In Substance Abuse Rehabilitation Programs NIDA-CTN-0009: Malcolm Reid, PhD New York Node

Smoking Abstinence

NIDA-CTN-0009 Summary of Findings and Recommendations Cigarette Smoking 10-12% quit rate 75% reduction in cigarettes/day reduced nicotine craving and withdrawal moderate treatment compliance, better at methadone programs Substance Abuse no change: primary substance of abuse abstinence rates treatment retention reduced craving with less smoking Should Programs Institute Smoking Cessation?YES

CTN Superheroes: Able to Leap Tall Buildings in a Single Bound and Complete Impossible Studies in Record Time

28 CTN 0028: Osmotic Methylphenidate (OROS-MPH) in Smokers with ADHD  Evaluate if treating ADHD with OROS-MPH vs. placebo increases the effectiveness of standard smoking treatment (i.e., nicotine patch and counseling) in adult smokers with ADHD  Evaluate the efficacy of OROS-MPH, relative to placebo, in treating ADHD in smokers with ADHD

CTN 0029: Osmotic Methylphenidate (OROS- MPH) in Adolescents with SUD and ADHD

OROS-MPH and ADHD Symptoms Significant decrease in ADHD symptoms and substance use over study period, but no between group differences Improvement in ADHD associated with decreased substance use ??? Effect of CBT 31

Summary/Discussion ADOLESCENT STUDIES Important information about use of meds in an understudied population SMOKING STUDIES Acceptability of addressing smoking in early recovery, meds in comorbid population BUPRENORPHINE Big win for CTN Demonstrated efficacy/tolerability in important populations not previously studied Longer tx is better outcomes than detox Improve penetrance/acceptability Pharmacogenetics/LFT data pending

CTN Pharmacotherapy: To Do List Cocaine Methamphetamine Marijuana Pharmacogenetics Combination therapy – meds plus specific behavioral tx Comorbidity Psychiatric comorbidity Medical comorbidity, including pain

What is the role of the CTN in Early Stage Pharmacotherapy Trials???

Thanks to all the study teams, community partners, study participants, CCTN and NIDA

Collaboration : The Whole is Greater Than The Sum of the Parts